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Abstract

The goal of this study is to create and assess an emulgel for the treatment of oral ulcers that contains clove oil, curcumin, and Argemone maxicana latex. Emulgels have emerged as a possibly useful delivery system for hydrophobic drugs. As a penetration booster, menthol was utilised, which also gives ulcers a cooling effect. Clove oil also serves this purpose. Herbal remedies with strong antiulcer properties include menthol, curcumin, and clove oil. While Argemone maxicana exhibits antimicrobial action, clove oil possesses anlgesic and antioxidant properties. While menthol offers cooling properties, curcumin, which is derived from curcuma longa, has anti-inflammatory and antibacterial properties. While menthol soothes mouth sores or ulcers. Diffusion tests, viscosity, spreadability, extrudability, and short-term stability were performed on five formulations. By the conclusion of the following analysis, the optimised formulation revealed that the medicines' respective releases—clove and curcumin—were 79 ± 3.2% and 72.07 ± 4.8%. The results of the investigation indicate that the emulgel has improved penetration properties and can be applied topically.

Keywords

Emulgel, volatile oils, herbal medicine, mouth ulcers, and oral sores

Introduction

One of the most prevalent disorders affecting the oral mucosa is oral ulceration. When the  An ulcer is the result of damage to the epithelium and lamina propria [1]. Oral ulcers have been found to be a symptom of several systemic disorders, such as inflammatory bowel disease. The kind, location, length, and frequency of systemic sickness have all been linked to the development of oral ulcers [2]. The peroral route is thought to be the most practical method of medicine administration by both patients and medical professionals [3]. The oral cavity's environment, which has a temperature of 37°C and a pH range of 5.75 to 7.05, acts as a buffer. Water makes up 99.5% of the oral fluid, while organic compounds and inorganic elements make up 0.3% and 0.2% of the fluid, respectively [4, 5]. There  A number of commercially available items, including as vitamin B12 tablets, mouthwash or spray containing benzydamine hydrochloride, steroid lozenges, and local anaesthetics, can be used to treat aphthous ulcers.[6] Commercially available dose forms have certain drawbacks, such as tablets that take longer to start working and mouthwashes that rinse quickly, which reduces the amount of medication that is effective [7]. Compared to emulgel, spray formulation waste occurs, and lozenges take longer to start working [8]. As their name implies, emulgels are a blend of emulsion and gel. Medicines are applied topically as water-in-oil and oil-in-water emulsions. They have a high degree of skin penetration.[9] The BCS classification systems state that emulgel is a better  choice for class II medications that have high permeability and poor solubility[10]. In this investigation, emulgel was prepared using herbal medications including curcumin and clove oil. composition. By blocking capsaicin receptors, clove oil derived from Syzygium aromaticum plants has strong analgesic and pain-relieving properties. [11] While menthol comes from the plants mentha piperita, it functions as a cooling agent. Curcumin is derived from Curcuma longa and inhibits the formation of prostaglandin, acting as an antimicrobial and anti-inflammatory to the mouth sores or ulcers [12, 13]. The gel phase was prepared using carbopol 940, a crosslinked polyacrylic acid polymer. It is a very powerful rheology modifier that can result in clear gels with high viscosity or hydro-alcoholic gels and shimmering creams [14, 15]. The goal of this study was to create, refine, and evaluate an emulgel including essential oils and herbal components to treat mouth ulcers while lessening the side effects of commercially available formulations, such as mouthwashes, sprays, and lozenges Many of the enormous variety of flowers are regarded as weeds or wild plants that have no commercial value and are therefore often overlooked. One such weed that proliferates widely throughout practically all of India and Rajasthan is Argemone mexicana L. Argemone mexicana, commonly known by the popular names Mexican poppy,Mexican pricly poppy, blooming thistle, cardo, cardosanto is a species of poppy found in Mexico and now widely naturalized in many regions of the world.

Local name – Mexican poppy.

Botanical name – Argemone maxicana.

Family – Papaveraceae.

Kingdom - Plantae.

Genus – Argemone.

Species – A. Mexicana.


 

 


Supplies and techniques

Materials:

propylene glycol, methyl paraben, span 80, tween 80, liquid paraffin, and carbopol 940 propyl paraben and triethanolamine (obtained at RJS College of Pharmacy'  Kokamthan).

 Honey, distilled water, Argemone maxicana latex  (from the stem of Argemone maxicana), clove oil ( from Extraction ) , and curcumin.

Research on preformulation

Identification by physical means

Clove oil, Argemone maxicana latex, and curcumin were found to be pure based on their physical state, colour, odour, melting point, boiling temperature, and acid value, among other organoleptic and physical characteristics.

Research on solubility

Through solubility experiments, the excipients to be included in the formulation were selected. Whether medications were soluble in liquid paraffin and propylene was evaluated qualitatively. distilled water, span 80, methanol, tween 80, and glycol.

Emulgel formulation

The gel's preparation

Using a mechanical stirrer set at 200 rpm, carbopol 940 was dissolved in purified water to create the gel phase of the emulgel formulation. After that, triethanolamine was used to modify the pH of the gel to a range of 6.0 to 6.8.

Emulsion preparation

The emulsion was prepared by taking the oil phase i.e. liquid paraffin as a solvent for clove oil (8% w/w) curcumin (0.2% w/w), menthol (5% w/w) a, span80 and Argemone maxicana latex in a beaker and in another beaker propylene glycol, methyl paraben and propyl paraben were taken. Then the required amount of water with honey was added in a beaker and tween80 was added in this water. Then both oil phase and aqueous phase were heated at 60- 70°C and mixed together with continuous stirring by mechanical stirrer at 200 rpm at room temperature, till the emulsion was formed.

Preparation of Emulgel

The emulgel was prepared by mixing the emulsion with gel in 1:1 ratio with continuous stirring by a mechanical stirrer at 200 rpm for 60 minutes. pH was adjusted by using  triethanolamine.


Table 1. Different emulgel formulation compositions (%w/w)

 


Emulgel Formulation Optimization

The amount of the polymer (Carbopol 940) and the ideal processing parameters (stirring speed and stirring time) were determined based on viscosity homogeneity, phase separation, and spreadability  , and the resulting emulgels were optimised


Table 2:  Optimization of Polymer Concentration based on Viscocity and Spreadability.


For additional research, the formulation with a concentration of 0.75 percent w/w of carbopol 940 was chosen or optimised, as it demonstrates optimal viscosity and good spreadability.

Process variable optimisation

200 rpm of stirring speed for 60 minutes was thought to be the ideal speed for emulgel formulation since formulation E5 displayed optimal viscosity, great homogenicity, and no phase separation.


Table 3. Optimization of stirring speed based on viscosity, phase separation and homogenicity


Table no 4. Optimization of stirring time based on viscosity, phase separation and homogenicity


The ideal stirring time for emulgel formulation was determined to be 60 minutes at 200 rpm, as formulation E2 demonstrated optimal viscosity, great homogenicity, and no phase separation.

Evaluation test for Emulgel.

Emulgel's physical characteristics

Using a digital pH meter, the colour, appearance, phase separation, homogeneity, and pH of each created mixture were examined visually.

Viscosity

The viscosity of produced formulations with spindle number 64s was measured at room temperature using a Brookefield digital viscometer running at 20 rpm for 10 minutes.

Spreadability

The spreadability of two glass slides was tested for emulgel compositions. The formulation whose spreadability was to be evaluated was spread across one slide, and the gel was sandwiched between the two by placing the other slide on top of it.  The slides were pressed together to eliminate any potential air before the adhering gel was removed. A 20 g weight was fixed firmly to the top slide. It was recorded how long it took the upper slide to fully separate from the lower slide.   where T is the time it takes to separate the slide, L is the length of the glass slide, and M is the weight attached to the upper slide.

Formula: S = M x L/T

Index of Swelling

1g of emulgel formulations were placed in a 50 ml beaker with 10 ml of distilled water, then covered with porous aluminium foil.

 In order to drain and weigh the external liquid, the samples were taken out of the beaker at different intervals and left undisturbed in a dry environment. The following formula was used to calculate the swelling index:

Swelling Index (SW)% = [ (Wt ? Wo)/Wo] × 100

Where,

(SW) % = Equilibrium percent swelling,

Wt = Weight of swollen emulgel after time t,

Wo = Original weight of emulgel at zero time.

 Extrudability

To determine the extrudability of emulgels, a closed, collapsable tube containing emulgel formulations was forcefully pushed at the crimped end. The mixtures were extruded till the pressure decreased.  following the removal of the cap. The weight was computed using grammes. required 10 seconds to extrude a 0.5 cm ribbon of the formulation.

Centrifugation testing for phase separation

Using centrifuge tubes, 6g of the emulgel mixture was placed and spun for 10 minutes at 4000 RPM. After ten minutes, every formulation was checked for the occurrence of phase separation.

Drug content

After dissolving 1g of emulgel in 10 ml of methanol, the mixture was filtered using Whatman filter paper. Next, 1 ml of the filtrate was placed in a volumetric flask containing 10 ml and diluted using  up to 10ml of methanol. Following that, the absorbance was measured using UV-Visible Spectroscopy at 277 nm,307 nm  to determine the relative contents of curcumin , clove oil.

RESULT AND DISCUSSION

Studies on pre-formulation

Drug identification by physical means

The physio-chemical features of the medications, such as clove oil and curcumin, were the focus of identification research. The liquid form of clove oil was pale yellow, while the scent of basil oil was sweet and spicy.  Curcumin was a golden powder with no smell. The melting and boiling points of curcumin powder (180- 182°C) and clove oil (148–250°C) were determined. Clove oil was found to have an acid value of 4.5.

Curcumin's Differential Scanning Calorimetry

Temperatures between 25 and 400 °C were used to measure curcumin's thermal behaviour. The DSC thermogram of curcumin indicated that its melting point was 170 °C.  curcumin. As Figure 1 makes evident, curcumin was thermally stable at temperatures below 180 °C.


Figure1. Fig. Differential scanning calorimetry of curcumin

 


Studies on solubility

The oil phase for emulgel production consisted of span80 and liquid paraffin since the medicines were miscible and soluble in these solvents.


Table 5. shows the solubility and miscibility various medications, such as clove oil and curcumin.

 

Emulgel evaluation

Emulgel's physical characteristics

The optimised mixtures produced a uniform, highly consistent yellowish emulgel.  thick, creamy mixture that isn't gritty.

Acidity

Because the pH of the oral cavity ranges from 6.5 to 6.8, the pH values of the optimised formulation E2 were determined to be 6.7, which is considered adequate to prevent the risk of irritation when applied to the oral mucosa.

Viscosity

The viscosities of formulas E1 through E5 were the lowest and greatest, respectively. The emulgels containing 1.5% w/w Carbopol 940 had the highest viscosity, whilst those with 0.25% w/w Carbopol 940 had the lowest. The viscosity of formulations increases with increasing polymer concentration while all other variables are held constant. The optimised formulation E2's viscosity was found to be 27500 ± 55.67cps.

Spreadability.

Spreadability is the rate at which the emulgel will cover the damaged tissue with the least amount of shear. The optimised formulation E2 was found to have a spreadability of 43.33 ± 0.33 inches.

Index of Swelling

Of all the formulations, the E5 emulgel with 1.5% w/w Carbopol 940 exhibited the highest swelling index. The swelling index value may be impacted by the polymer's chain strength and degree of water absorption. The optimised formulation E2 was found to have a swelling index of 65 ± 0.5%.

Capability to Extrude

The optimised formulations E2 exhibited excellent extrudability, indicating that the emulgel has outstanding flowability.

Centrifugation testing for phase separation

The optimised formulation E2 showed no signs of phase separation, demonstrating the product's stability at high shear rates.

Emulgel's drug content

The optimised formulations E2's medication content was ascertained. Clove oil and curcumin were determined to have a percentage drug concentration of 97.07 ± 2.1%, 95.91 ± 1.9%, and 96.22 ± 2.0%, respectively. It indicates that the medication was dispersed evenly throughout the compounds.

CONCLUSION

The results of this study indicate that an emulgel containing eugenol, clove oil, Argemone maxicana latex, and curcumin can be applied topically for the local treatment of  mouth sore. The topical emulgel also showed promising medication release and penetration properties, which is an added bonus. The presence of clove oil, Argemone maxicana latex, and curcumin in the gel dosage form facilitates easier application to the oral mucosa. The primary obstacle to the drug's gel formulation is its hydrophobic nature, which calls for additional research on the drug's therapeutic efficacy.

ADHERENCE TO MORAL PRINCIPLES

RECOGNITIONS.

New Delhi is home to the All India Council of Technical Education (AICTE).

REFERENCES

  1. Patil SV, Rukari TG, Redkar MR. The Emulgel is a contemporary topical medication delivery technique.Jan 29, 2019; World J. Pharm. Res. 8(4): 586–597.
  2. Guénette SA, Vachon P, Beaudry F, Marier JF, Ross A. The effects of eugenol on rats with thermal hypersensitivity and its pharmacokinetics. Eur. J. Pharmacol.;562(1-2):60-67; May 7, 2007.
  3. Chaudhuri PK, Singh D. An overview of the pharmacological and phytochemical characteristics of basil (Ocimum sanctum L.). On August 1, 2018, Ind. Crops. Prod. 118:367–382.
  4. Darwhekar GN, Chouhan S, Shahare N. A survey of herbs used to cure mouth ulcers.  2021 Jul 29; IJPC: 68–74.
  5. Ale SI, Maibach HI, Hostþnek JJ. A review of the sensitisation potential of menthol. Exo. Dermatology. 2002;1(2):74–80.
  6. Sirivat A, Vayumhasuwan P. Carbopol 940 gel viscoelastic characteristics and their connections to gel bases' piroxicam diffusion coefficients. Dec. 2005;22(12):2134–2140; Pharm. Res.
  7. de Souza Mendes PR, F. Naccache M, M. Costa C, S. Fonseca B, and R. Varges P.  Carbopol® dispersions in water and in water/glycerol solutions are characterised rheologically. Fluids, Jan. 4, 2019; 4(1):3–20.
  8. Ahmed MH, Hussien MO, Mohammed NH. qualitative examination of Syzygium aromaticum (L) (clove) essential oil by means of gas chromatography-mass spectrometry (GC-MS). 2015;5(2):350–354. IJRPC.
  9. Jafarizadeh-Malmiri H, Sayyar Z. Using several thermodynamic models, examine how temperature affects the solubility of curcumin O/W nanodispersions and thermodynamic parameters. Food Eng. Int. J. 2019 Feb 1;15:1-2.
  10. Sah SK, Badola A, Mukhopadhyay S. Tioconazole-loaded emulgel development and assessment. 2017; Int. J. Appl. Pharm. 9:83–90.
  11. Khan AW, Kumar A, Sharma RK, Kotta S, Ansari SH, Ali J. Aloe vera gel formulation, optimisation, and assessment for wound healing. Oct. 2013, Pharmacogn. Mag. 9(Suppl 1): S6–S10.
  12. Gowda DV, Shivakumar HG, Reddy SC, Navya M, Maheshwari PV, and Varma VN.  delivery of calcipotriol as an emulgel for efficient skin penetration. Dec. 1, 2014; 22(6):591–599; Saudi Pharm. J.
  13. Khalil MM, Mahdy H, Sabry DY, and Ismail EH. Synthesis, Properties, and Anticancer Uses of a Few Ternary Metal Complexes of Curcumin with 1, 10-phenanthroline. 2014 Aug 26;6(3):509–519 in J. Sci. Res.
  14. Pramod K, Suneesh CV, Shanavas S, Ansari SH, Ali J. Systematic drug-excipient compatibility investigations reveal eugenol's compatibility with formulation excipients. 2015 Dec;6(1):1-4; J. Anal. Sci. Technol.
  15. Leão JC, Gomes VB, Porter S. An update for general practitioners on ulcerative lesions of the mouth. Clinics, 62:769–780, 2007.
  16. Challacombe SJ, J. Mestecky, Shirlaw PJ, Lamm ME, W. Strober, J. Bienenstock, J. McGhee JR, and L. Mayer. Immunology of oral cavity disorders. Section 89. Immune responses in the local area to TB, 2005; 1517–1546.
  17. Wolff A, Giannola LI, Campisi G, Ciach T, Velten T, Scholz OA, and Schumacher A. Oral drug delivery: a new mechatronic delivery system is the emphasis. Drug Discovery Today. Mar. 1, 2008;13(5-6):247–253.
  18. [18] Pickel FD, Cort W, Starr N, Bilotti A, Pigman W. Evaluation of enamel-rehardening agents in saliva. J. Dent. Res. 1965 Sep;44(5):855-859.
  19. Relationship between caries and plaque in saliva. Dent. Res. J. 1974 Mar;53(2):246-266
  20. Adinarayana S., Ahmed MG. Hydrocortisone film formulation for the management of pharyngitis. Sep. 2019, Turk. J. Pharm. Sci. 16(3):348-355.
  21. Motallebnejad M, Kazemi S, Rahmani F, Moghadamnia AA, and Shirzad A. A randomised double-blind crossover clinical trial was conducted to examine the impact of 0.5% chitosan mouthwash on recurrent aphthous stomatitis. 
  22. Golestannejad Z, Motamedi MR. Phthalous ulcers can be treated with pure nicotine. 2015 Apr 5;12(2):197-198; Dent. Res. J
  23. Shukla A, Tiwari A, Mishra MK, Yadav SK. Emulgel: a novel method for improved topical medication administration. Pharm. Res. Int. J. Curr. 2016;9(1):15–19.
  24. World Journal of Biology, Pharmacy, and Health, edited by Surendra Ahirwar and Dharmendra Jain  sciences
  25. Argemone maxicana L:, Afroz Alam and Adnan Khan, Annals of Phytomedicine: An International Journal. A herb with a wide range of pharmacological and therapeutic uses.

Reference

  1. Patil SV, Rukari TG, Redkar MR. The Emulgel is a contemporary topical medication delivery technique.Jan 29, 2019; World J. Pharm. Res. 8(4): 586–597.

 

  1. Guénette SA, Vachon P, Beaudry F, Marier JF, Ross A. The effects of eugenol on rats with thermal hypersensitivity and its pharmacokinetics. Eur. J. Pharmacol.;562(1-2):60-67; May 7, 2007.
  2. Chaudhuri PK, Singh D. An overview of the pharmacological and phytochemical characteristics of basil (Ocimum sanctum L.). On August 1, 2018, Ind. Crops. Prod. 118:367–382.
  3. Darwhekar GN, Chouhan S, Shahare N. A survey of herbs used to cure mouth ulcers.  2021 Jul 29; IJPC: 68–74.
  4. Ale SI, Maibach HI, Hostþnek JJ. A review of the sensitisation potential of menthol. Exo. Dermatology. 2002;1(2):74–80.
  5. Sirivat A, Vayumhasuwan P. Carbopol 940 gel viscoelastic characteristics and their connections to gel bases' piroxicam diffusion coefficients. Dec. 2005;22(12):2134–2140; Pharm. Res.
  6. de Souza Mendes PR, F. Naccache M, M. Costa C, S. Fonseca B, and R. Varges P.  Carbopol® dispersions in water and in water/glycerol solutions are characterised rheologically. Fluids, Jan. 4, 2019; 4(1):3–20.
  7. Ahmed MH, Hussien MO, Mohammed NH. qualitative examination of Syzygium aromaticum (L) (clove) essential oil by means of gas chromatography-mass spectrometry (GC-MS). 2015;5(2):350–354. IJRPC.
  8. Jafarizadeh-Malmiri H, Sayyar Z. Using several thermodynamic models, examine how temperature affects the solubility of curcumin O/W nanodispersions and thermodynamic parameters. Food Eng. Int. J. 2019 Feb 1;15:1-2.
  9. Sah SK, Badola A, Mukhopadhyay S. Tioconazole-loaded emulgel development and assessment. 2017; Int. J. Appl. Pharm. 9:83–90.
  10. Khan AW, Kumar A, Sharma RK, Kotta S, Ansari SH, Ali J. Aloe vera gel formulation, optimisation, and assessment for wound healing. Oct. 2013, Pharmacogn. Mag. 9(Suppl 1): S6–S10.
  11. Gowda DV, Shivakumar HG, Reddy SC, Navya M, Maheshwari PV, and Varma VN.  delivery of calcipotriol as an emulgel for efficient skin penetration. Dec. 1, 2014; 22(6):591–599; Saudi Pharm. J.
  12. Khalil MM, Mahdy H, Sabry DY, and Ismail EH. Synthesis, Properties, and Anticancer Uses of a Few Ternary Metal Complexes of Curcumin with 1, 10-phenanthroline. 2014 Aug 26;6(3):509–519 in J. Sci. Res.
  13. Pramod K, Suneesh CV, Shanavas S, Ansari SH, Ali J. Systematic drug-excipient compatibility investigations reveal eugenol's compatibility with formulation excipients. 2015 Dec;6(1):1-4; J. Anal. Sci. Technol.
  14. Leão JC, Gomes VB, Porter S. An update for general practitioners on ulcerative lesions of the mouth. Clinics, 62:769–780, 2007.
  15. Challacombe SJ, J. Mestecky, Shirlaw PJ, Lamm ME, W. Strober, J. Bienenstock, J. McGhee JR, and L. Mayer. Immunology of oral cavity disorders. Section 89. Immune responses in the local area to TB, 2005; 1517–1546.
  16. Wolff A, Giannola LI, Campisi G, Ciach T, Velten T, Scholz OA, and Schumacher A. Oral drug delivery: a new mechatronic delivery system is the emphasis. Drug Discovery Today. Mar. 1, 2008;13(5-6):247–253.
  17. [18] Pickel FD, Cort W, Starr N, Bilotti A, Pigman W. Evaluation of enamel-rehardening agents in saliva. J. Dent. Res. 1965 Sep;44(5):855-859.
  18. Relationship between caries and plaque in saliva. Dent. Res. J. 1974 Mar;53(2):246-266
  19. Adinarayana S., Ahmed MG. Hydrocortisone film formulation for the management of pharyngitis. Sep. 2019, Turk. J. Pharm. Sci. 16(3):348-355.
  20. Motallebnejad M, Kazemi S, Rahmani F, Moghadamnia AA, and Shirzad A. A randomised double-blind crossover clinical trial was conducted to examine the impact of 0.5% chitosan mouthwash on recurrent aphthous stomatitis. 
  21. Golestannejad Z, Motamedi MR. Phthalous ulcers can be treated with pure nicotine. 2015 Apr 5;12(2):197-198; Dent. Res. J
  22. Shukla A, Tiwari A, Mishra MK, Yadav SK. Emulgel: a novel method for improved topical medication administration. Pharm. Res. Int. J. Curr. 2016;9(1):15–19.
  23. World Journal of Biology, Pharmacy, and Health, edited by Surendra Ahirwar and Dharmendra Jain  sciences
  24. Argemone maxicana L:, Afroz Alam and Adnan Khan, Annals of Phytomedicine: An International Journal. A herb with a wide range of pharmacological and therapeutic uses.

Photo
Sakshi Labhade.
Corresponding author

Students, RJS College Of Pharmacy, Kokamthan, Kopargaon, Ahmednagar, Maharashtra, India.

Photo
Kanchan Gursal
Co-author

Assistant Professor, Department Of Pharmaceutics, RJS College Of Pharmacy, Kokamthan, Kopargaon, Ahmednagar, Maharashtra, India.

Photo
Bahaisti Patel
Co-author

Students, RJS College Of Pharmacy, Kokamthan, Kopargaon, Ahmednagar, Maharashtra, India.

Photo
Rutuja shirode
Co-author

Students, RJS College Of Pharmacy, Kokamthan, Kopargaon, Ahmednagar, Maharashtra, India.

Photo
Roshni sayyad
Co-author

Students, RJS College Of Pharmacy, Kokamthan, Kopargaon, Ahmednagar, Maharashtra, India.

Photo
Tanuja kadam
Co-author

Students, RJS College Of Pharmacy, Kokamthan, Kopargaon, Ahmednagar, Maharashtra, India.

Photo
Shubham Bodkhe
Co-author

Students, RJS College Of Pharmacy, Kokamthan, Kopargaon, Ahmednagar, Maharashtra, India.

Sakshi Labhade ,Kanchan Gursal ,Bahaisti Patel, Rutuja Shirode, Roshni Sayyad ,Tanuja Kadam ,Shubham Bodkhe, Preparation And Evaluation Of Herbal Emulgel, Int. J. of Pharm. Sci., 2024, Vol 2, Issue 10, 1764-1771. https://doi.org/10.5281/zenodo.14013733

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